key: cord-0739310-7mnd6y67 authors: Yau, Yuk Kam; Mak, Wing Yan Joyce; Lui, Nok Shun Rashid; Ng, Wai Yin Rita; Cheung, Choi Yan Kitty; Li, Ying Lee Amy; Ching, Yuet Ling Jessica; Chin, Miu Ling; Lau, Ho Shing Louis; Chan, Ka Leung Francis; Chan, Kay Sheung Paul; Ng, Siew Chien title: High prevalence of extended‐spectrum beta‐lactamase organisms and the COVID‐19 pandemic impact on donor recruitment for fecal microbiota transplantation in Hong Kong date: 2021-10-08 journal: United European Gastroenterol J DOI: 10.1002/ueg2.12160 sha: ae2139005729754fb61d692f1b42bf5f722e427e doc_id: 739310 cord_uid: 7mnd6y67 BACKGROUND: With increasing number of clinical trials relating to fecal microbiota transplantation (FMT), it is crucial to identify and recruit long‐term, healthy, and regular fecal donors. OBJECTIVE: We aimed to report the outcomes of screening and recruitment of fecal donors for FMT. METHODS: Potential donors were recruited via advertisement through internal mass emails at a university. They were required to undergo a pre‐screening telephone interview, a detailed questionnaire, followed by blood and stool investigations. RESULTS: From January 2017 to December 2020, 119 potential donors were assessed with 75 failed pre‐screening. Reasons for failure included: inability to come back for regular and long‐term donation (n = 19), high body mass index (n = 17), underlying chronic illness or on long‐term medications (n = 11), being healthcare professionals (n = 10), use of antibiotics within 3 months (n = 5) and others (n = 13). Forty‐four donors completed questionnaires and 11 did not fulfill the clinical criteria. Of the remaining 33 potential donors who had stool and blood tests, 21 failed stool investigations (19 extended‐spectrum beta‐lactamase [ESBL] organisms, one Clostridioides difficile, one C. difficile plus Methicillin Resistant Staphylococcus aureus), one failed blood tests (high serum alkaline phosphatase level), one required long‐term medication and nine withdrew consent and/or lost to follow‐up. In total, only one out of 119 (0.8%) potential donors was successfully recruited as a regular donor. CONCLUSION: There was a high failure rate in donor screening for FMT. Main reasons for screening failure included high prevalence of positive ESBL organisms in stool and failed commitment to regular stool donation. Fecal microbiota transplantation (FMT) is defined as infusion of stool from healthy donors to rectify the recipient's intestinal microbial community by introducing micro-organisms associated with a "healthy" state to normalize microbiota composition and function. Currently, FMT is recognized as an effective and approved therapy for recurrent or refractory Clostridioides difficile infection (CDI) with a cure rate of around 90% in patients who did not respond to antibiotic therapy. [1] [2] [3] There is a growing body of literature exploring the efficacy of FMT in treating other gastrointestinal diseases, including inflammatory bowel disease (IBD), 4 irritable bowel syndrome, 5 chronic constipation 6 and pouchitis, 7 etc. Moreover, FMT has been used for treatment of diseases beyond the gastrointestinal tract, including metabolic diseases like diabetes mellitus (DM), obesity, neurological disorders like Parkinson's disease and autism etc. [8] [9] [10] [11] Thus, there is a huge demand for FMT donors. With the increasing demand for FMT in daily practice and clinical trials, a recent international consensus on stool banking for FMT has been developed. 12 13 In June 2019, the Food and Drug Administration (FDA) of the United States has issued a safety alert regarding the use of FMT in immunocompromised patients, as two immunocompromised adults who received investigational FMT developed invasive infections caused by extendedspectrum beta-lactamase (ESBL)-producing E. coli, with one case of fatality. 14 Therefore, it is crucial to develop a standardized screening process for FMT donors to ensure safety. December 2019, there has been concerns about the risk of fecal transmission of SARS-CoV-2 virus. 15 In view of this potential risk, the FDA has issued another alert on additional screening procedures for COVID-19 symptoms and stool for SARS-CoV-2 RNA before donation in April 2020. 16 We aimed to report the screening procedure, characteristics, and outcomes of our FMT donors in Hong Kong. Potential donors were identified mainly by personal referral from staff or from advertisement through the internal mass email system of the Chinese University of Hong Kong, Hong Kong. There were three parts of the screening process. Part 1 is a prescreening by phone interview for potential donors to assess for preliminary eligibility. During pre-screening, questions asked included body mass index (BMI), chronic illnesses, any regular usage of medication, any usage of antibiotics within three months, family history of colon cancer or IBD in first-degree relatives, any regular contact with patients or clinical specimen and the availability for regular stool donation in the long-term (Table S1 ). Part 2 is a questionnaire-based assessment. All potential donors needed to complete two questionnaires after they passed the prescreening procedures. Potential donors' information on risk of infectious disease, bowel habits and history of gastrointestinal disease, past medical history and medications used, family history, travel history and social history were collected via questionnaires (Table 1) . All procedures were conducted in the Center for Gut Microbiota Research located in the Prince of Wales Hospital, The Chinese University of Hong Kong. Donor inclusion criteria were adults between 18 and 50 years old, with normal body weight (18 < BMI < 23), and without any chronic diseases, which is defined as any condition that last 1 year or more and require ongoing medical attention and/or limit activities of T A B L E 1 Screening criteria of potential fecal donors Potential donors will be excluded from donation if they: year if they continue to be donors after 1 year. This is to ensure the health of the donors and the safety of the FMT stool bank. If the donor develops a new medical condition during follow-up, he/she will be suspended from stool donation according to physicians' discretion and the samples will be withdrawn from the stool bank. The whole donor screening procedure is shown in Figure 1a . Since would be used for FMT procedure (Figure 1a) . Besides, additional screening measures for SARS-CoV-2 (Table 3) were implemented in July 2020 to further enhance the safety. All DTS and stool for SARS-CoV-2 testing were also repeated. If any of the above tests failed, the whole batch of donor stool from the same donor would be discarded (Figure 1b) . A total of 119 potential donors were assessed for eligibility from January 2017 to December 2020 ( Figure 2 ). There were 49 males and ranged from 0% to 100% in each donor (Figure 3a) . We also arranged ESBL-organism testing for recipients, who were selected for FMT according to three indications that is a randomized controlled trial for DM or obesity, a pilot study for IBD and recurrent C. difficile. The percentage of recipients screened to be ESBL positive was 60%, 50% and 50% in the three groups respectively (Figure 3b ). none of the 571 potential stool donors were tested positive for ESBLproducing organisms in stool. 28 The high rate of ESBL-E fecal colonization in Hong Kong can be explained by several factors, including a densely packed population, high turnover of travelers, geographical close proximity with mainland China and Southeast Asia, and the consumption of raw vegetables, poultry and retail chicken meat. [35] [36] [37] As Hong Kong is in the area with high ESBL-E carriage, this is a significant barrier for donor recruitment. To overcome this, we now provide dietary suggestions to potential donors who are due for screening and donation to reduce the rate of exposure to ESBLproducing organisms via specific food consumption. 38 We also and Thailand. 39 Donors with consumption of two or more courses of antibiotics within 6 months were also excluded from stool donation so as to lower the risk of ESBL-E carriage. 34 Besides, another potential solution to the high failure rate due to ESBL-E positivity is to apply the concept of patient-donor CMV matching in the context of hematopoietic stem cell transplantation ( proportion of ESBL positive samples than pork (12.1%) and beef (4.2%). 38 The Consumer Council in Hong Kong also found that over 60% of chicken meat in market were found to be containing ESBLproducing bacteria. 53 Therefore, in the future, we could advise all potential donors to consume less chicken meat and to cook the meat thoroughly and be careful when handling raw meat and Table 4 . One of the strengths of this study is that the data was collected from an institution which has offered FMT for the past 3 years, and provides real-world data on donor screening and recruitment. In addition, all the screening procedures were performed in house, allowing us to access the data with regard to all facets of FMT screening. There are also some limitations in this study: first, the number of applicants was quite limited. Additionally, the inter-individual stool heterogeneity should not be neglected even though we have used the same criteria to select eligible donors. Gut microbiota in each individual is complex and consists of different species of bacteria and non-bacterial microbes like virus, fungi, Archaea and parasites. For example, one donor may have the components efficacious in treating CDI but not IBD. 54 However, the link between specific components of stools from healthy donors and the treatment efficacy has yet to be fully elucidated. 55 In conclusion, it is hard to recruit regular and healthy donors for FMT with a high failure rate during the screening process. With the expanding indications and clinical trials of FMT, it is pressing to standardize and improve stool donor screening procedures to ensure safety for patients, and to achieve a higher donor recruitment rate so as to ensure the sustainability of such services. 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